FDA mandates approval for all pancreatic enzyme replacements

The Cystic Fibrosis Foundation has announced its support of the Food and Drug Administration's (FDA) requirement that manufacturers of pancreatic enzyme replacements obtain FDA approval for their products within the next four years. This rule allows enzyme products to remain available to patients during that time. At the CF Foundation's urging, an FDA review found that inconsistencies in the formulation, dosage and manufacturing processes of many enzymes could significantly compromise both the safety and effectiveness of the drugs in patients with pancreatic diseases, including cystic fibrosis (CF).

The CF Foundation has received several reports of treatment failure after pharmacists supplied a substitute enzyme in place of that prescribed by the physician. Approximately 90 percent of people with CF require supplementation with enzymes and rely on the predictability of a known dose of a specific pancreatic enzyme product. Variations in the active ingredients can alter therapeutic impact and result in undesirable side effects such as malabsorption and constipation.

The enzyme products available on the market today have never received FDA approval because pancreatic enzymes predate the 1938 passage of the FDA approval act. The FDA has allowed these products to be "grandfathered" and to remain on the market because of their lifesaving benefits for patients. The lack of quality and consistency in many enzyme products, however, has brought this lack of approval into question and has stimulated this mandate. It gives manufacturers four years to obtain FDA approval, during which time their products will continue to be available to patients, unless the manufacturer voluntarily withdraws its product.

The CF Foundation strongly encouraged the FDA to initiate a review of enzyme products to aid patient safety.  Before the recent FDA decision, the CF Foundation alerted CF care center staff members, as well as patients and families, to the importance of non-substitution of enzyme prescriptions. Leslie Hendeles, Pharm.D., professor of pharmacy and pediatrics at the University of Florida, also was instrumental in the success of this initiative.

"This decision is a positive one for the thousands of individuals affected by CF. Proper digestion and absorption of food and nutrients is so important in people with CF; if they are not using products with reliable performances, their digestion and their health suffer as a result," said Hendeles. "This standardization of enzymes will eliminate unreliable products and lead to accurate product knowledge for patients, families and the healthcare professionals who treat them."

According to the FDA, there are 23 manufacturers and 26 repackers marketing 38 enzyme formulations. To streamline the approval process, the FDA has published a guidance document that will assist manufacturers of pancreatic enzyme preparations with drafting and submitting applications for approval of their products. Until FDA approval has been secured, patients will continue to have access to their traditional enzymes as long as they remain on the market, thereby preventing a sudden change to a delicate healthcare regimen.

"This decision by the FDA is a victory for the CF Foundation and for all people with CF. Prescribing enzymes should not have to be a 'guessing game' for patients, doctors or pharmacists," said Robert J. Beall, Ph.D., president and CEO of the CF Foundation. "Patients should be able to rest assured that their medication is the right dosage for them and that it will bolster their health, not hinder it. We applaud the FDA for this mandate and hope that all pancreatic enzyme manufacturers will take action immediately to obtain FDA approval to establish the consistency and dosage of their products."

Until all manufacturers have acquired FDA approval, pharmacists should be aware of the production variances, the allowable limits in product content and the inequality of certain pancrelipase products. Additionally, pharmacists should not provide a substitute pancreatic enzyme without first contacting the prescriber, until FDA-approved bioequivalent generic products become available.

CF is a genetic disease that affects approximately 30,000 people in the United States.  A defective gene causes the body to produce abnormally thick, sticky mucus that leads to chronic and life-threatening lung infections and impairs digestion.  When the CF Foundation was created in 1955, few children lived to attend elementary school.  Today, because of research and care supported by the CF Foundation with money raised through donations from individuals, corporations and foundations, the median age of survival for people with CF is in the early 30s.